Short-Term Potentiation of Miniature Excitatory Synaptic Currents Causes Excitation of Supraoptic Neurons

Abstract

Magnocellular neurons (MCNs) of the hypothalamic supraoptic nucleus (SON) secrete vasopressin and oxytocin. With the use of whole-cell and nystatin-perforated patch recordings of MCNs in current- and voltage-clamp modes, we show that high-frequency stimulation (HFS, 10-200 Hz) of excitatory afferents induces increases in the frequency and amplitude of 2,3-dioxo-6-nitro-1,2,3, 4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide (NBQX)-sensitive miniature excitatory postsynaptic currents (mEPSCs) lasting up to 20 min. This synaptic enhancement, referred to as short-term potentiation (STP), could be induced repeatedly; required tetrodotoxin (TTX)-dependent action potentials to initiate, but not to maintain; and was independent of postsynaptic membrane potential, N-methyl-D-aspartate (NMDA) receptors, or retrograde neurohypophyseal neuropeptide release. STP was not accompanied by changes in the conductance of the MCNs or in the responsiveness of the postsynaptic non-NMDA receptors, as revealed by brief application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate. mEPSCs showed similar rise times before and after HFS and analysis of amplitude distributions of mEPSCs revealed one or more peaks pre-HFS and the appearance of additional peaks post-HFS, which were equidistant from the first peak. STP of mEPSCs was not associated with enhanced evoked responses, but was associated with an NBQX-sensitive increase in spontaneous activity of MCNs. Thus we have identified a particularly long-lasting potentiation of excitatory synapses in the SON, which has a presynaptic locus, is dissociated from changes in evoked release, and which regulates postsynaptic cell excitability.

Retrograde Regulation of GABA Transmission by the Tonic Release of Oxytocin and Endocannabinoids Governs Postsynaptic Firing

“…In ϳ30% of the trials, this stimulation protocol resulted in robust increase in the frequency of quantal IPSCs. This effect has been reported previously in the hypothalamus for excitatory synapses (Kombian et al, 2000a). This increase in GABA IPSC frequency can outlast the stimulus train and can lead to a substantial membrane hyperpolarization.…”

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

“…This observation is in line with the proposed reliance of asynchronous release on residual Ca 2ϩ . At glutamate synapses on MNCs in the supraoptic nucleus, short-term potentiation of glutamate release has been described previously in response to high-frequency tetanization of afferents (Kombian et al, 2000). It is not clear whether this is a unique phenomenon or whether it reflects a buildup of successive asynchronous release events.…”

Action Potential-Independent Release of Glutamate by Ca2+Entry through Presynaptic P2X Receptors Elicits Postsynaptic Firing in the Brainstem Autonomic Network

“…1 B, 3B4 ). Fourth, if the large amplitude is caused by spatial summation of independently occurring events at distinct sites, the time from the event onset to the peak (i.e., rise time) should be longer than non-large events, because of weaker synchronization of release timing (Kombian et al, 2000;Sharma and Vijayaraghavan, 2003); however, this was not the case with the large minis (Fig. 4C, interval between vertical broken lines).…”